Toxicology Week 2 Flashcards
What toxidrome is seen with TCA overdose?
Anticholinergic
What are S/S of anticholinergic toxidrome?
Increased BP -> abrupt decrease in BP
Increased HR -> normal to decreased BP
Increased temperature
Rapid decline in mental status
EKG signs of TCA toxicity
- QRS widening
- R wave amplitude
Seizures possible
TCA toxicity treatments
Sodium channel blockade reversal***
- Hypertonic sodium
AND/OR
- Alkalinization
Both: sodium bicarbonate
Goals of sodium bicarb treatment
- QRS narrowing
- Blood pH <7.55
How do we treat anticholinergic effects of TCA overdose?
DONT
What are treatments for dysrhythmia in TCA overdose?
Magnesium, lidocaine
What are treatments for hypotension in TCA overdose?
Norepinephrine, epinephrine, vasopressin
Last resort: methylene blue, lipid emulsion, high dose insulin
What are treatments for seizures in TCA overdose?
Benzodiazepines*, barbiturates
NOT PHENYTOIN
Why should you not use phenytoin in TCA overdose?
Increase frequency and duration of VT
Why should you not use flumazenil?
Blocks benzo, ruins protection against seizures
What are possible TCA decontamination strategies?
Orogastric lavage, charcoal
What toxidrome is seen in bupropion overdose?
Sympathomimetic (amphetamine backbone)
What are S/S of a sympathomimetic toxidrome?
Increased HR, BP
Miscellaneous signs of bupropion toxicity
- Delayed seizures
- Widened QRS
T/F: You should avoid sodium bicarbonate in bupropion toxicity
TRUE: not responsive
Bupropion overdose complications
- Sympathomimetic crisis
- Lazarus effect
- Cardiogenic shock
- Status epilepticus
- Death
Bupropion overdose treatments
Decontamination: activated charcoal*
Supportive care: treat BP with benzo*, lipid emulsion? ECMO?
Which type of decontamination can be used for severe bupropion overdose or if it’s outside the charcoal window?
Whole bowel irrigation
SSRI overdose treatment
Supportive care, monitoring
Benzo for BP/tremors
Antidote: cyproheptadine
Which SSRI is most likely to cause seizures?
Citalopram (ECG abnormalities can be delayed)
SSRI overdose S/S?
Diaphoresis, hyperthermia, incoordination, spontaneous clonus, agitation, tremor, diarrhea, mental status changes
What is the progression of digoxin toxicity effects?
GI effects (N/V, diarrhea)
->
CNS effects (headaches, confusion, delirium, visual halos)
->
Metabolic effects (hyperkalemia)
What are pre-distribution effects of digoxin toxicity?
- N/V
- Hyperkalemia
What are post-distribution effects of digoxin toxicity?
- Hypotension
- Bradycardia
- Dysrhythmias
- Death
What K should we aim for in hyperkalemia?
K < 5 mEq/mL
What EKG effects are signature of digoxin?
- Prolonged PR interval
- Salvador Dali’s mustache
Digoxin toxicity treatments
Decontamination (activated charcoal - repeat doses in renal failure)
Hyperkalemia treatment (Digoxin immune FAB, calcium)
What is the major concern with calcium treatment in digoxin hyperkalemia treatment?
Stone heart
Which digoxin immune FAB formulation has a higher Vd and less allergies?
Fc fraction cleaved
What are the indications for Digifab?
- K > 5 mEq/L
- Level > 20 mcg/L
- Progressing signs of toxicity
What is the antidysrhythmic of choice without Digifab?
Phenytoin
How do you dose Digifab acutely if you know their dose?
1 vial bind 0.5mg of digoxin
cp = dose/Vd
#vials = level * Wt(kg)/100 - round up
How do you dose Digifab acutely if their dose of digoxin was unknown?
10 vials for adults AND children
When should Digifab be used for known-dose chronic digoxin toxicity?
Post-distribution level of >6 mcg/L
Progressing or severe signs of toxicity
How much Digifab should be given for unknown dose chronic digoxin toxicity?
5 vials for adults
3 vials for children
Acute Digifab dosing in clinical practice
Give 2 vials and titrate to effect (Q1H without response)
Chronic Digifab dosing in clinical practice
Give 1-2 vials and titrate to effect (Q1H without response)
How do you calculate anion gap?
Na - (Cl + HCO3)
What is a normal anion gap?
4 - 12
Alcohols of interest
Methanol
Ethylene Glycol
Isopropanol
How do toxic alcohols present?
- Altered mental status
- GI distress
- Specific differences between alcohols
What are examples of methanols?
- Gas-line antifreeze
- Windshield washer fluid
- Denaturants
(High volatility)
What are some examples of ethylene glycol?
- Automobile coolant
- Solvents
- De-icers
- Air conditioning units
(Low volatility)
What are some early signs of toxic alcohols?
- GI distress/inebriation
What are the later signs of methanol toxicity?
- High anion gap metabolic acidosis
- Visual changes
What are the later signs of ethylene glycol toxicity?
- High anion gap metabolic acidosis
- Nephrotoxicity*
- Hypocalcemia
What can we consider for toxic alcohol treatment initially?
Decontamination? (activated charcoal, lavage, irrigation)
Electrolytes and ABG
Ethanol level
Methanol and ethylene glycol level - delayed*
Measured osmolality
Consider ADH inhibition
What ADH inhibitors we can use?
Ethanol
4-methylpyrazole (Fomepizole - Antizol)
What is the maintenance goal of ethanol treatment?
BAC of 100 mg/dL
What are possible side effects of fomepizole?
Headache nausea, dizziness, minor allergic reactions
How is fomepizole dosed?
Loading dose of 15 mg/kg
2nd phase given 10 mg/kg Q12H x4 doses
Maintenance of 15 mg/kg Q12H
What substances can be given if the alcohol ingested is unknown?
- Folic acid
- Thiamine
- Vitamin B6 (pyradoxime)
- Magnesium
Shifts metabolic pathway of alcohols
What can be given to correct acidosis?
Sodium bicarbonate
When should hemodialysis be used for toxic alcohols?
- Methanol or ethylene glycol 25-50 mg/dL
- High osmol gap without another cause
- End organ manifestations of toxicity
- Sever metabolic acidosis
Levels may be delayed… what can be an early indicator for toxic alcohols?
Osmol gap
How do you calculate osmol gap?
2Na + BUN/2.8 + Glucose/18 + Alcohol/N = calculated osmolality
Osmol gap = measured - calculated
High gap? likely a toxic alcohol
What is a normal osmol gap?
-14 to 10
What should be ruled out during increased anion gap before determining it’s a toxic alcohol?
- Ketones
- Lactate
- Worsened renal function
What is the “safest” toxic alcohol that we are less worried about?
Propylene glycol
Isopropyl alcohol
- Very inebriating and irritating
- GI bleeding possible
- Metabolized to acetone
Which supplement(s) is/are helpful in methanol treatment?
Folic acid
Which supplement(s) is/are helpful in ethylene glycol treatment?
Thiamine, Vitamin B6, Magnesium
What are CB1 receptors involved with?
CNS
GPCRs
Motor activity
Thinking
Pain perception
What are CB2 receptors involved with?
Periphery
GPCRs
Immune modulation
Anti-inflammatory
What is the major psychoactive component of marijuana?
THC (CB1 partial agonism)
What lab abnormalities can be caused by synthetic cannabinoids?
- Low potassium
- Hyperglycemia
- Increased creatinine kinase*
- Increased WBC*
- Increase creatinine*
What are common s/s of synthetic cannabinoids?
- Agitation
- Seizures
- N/V
- Dehydration
- HTN
- Tachycardia
(Adrenergic)
What supportive care can be given to treat agitation in synthetic cannabinoids?
IV benzodiazepines
Consider antipsychotics (haloperidol, olanzapine, droperidol)
What supportive care can be given to treat seizures in synthetic cannabinoids?
IV benzodiazepines
Consider anti-epileptics later on (status epilepticus)
What supportive care can be given for dehydration in synthetic cannabinoids?
IV crystalloids
What supportive care can be given for hypertension/tachycardia in synthetic cannabinoids?
IM/IV benzodiazepines first
IV antihypertensives PRN
What is the diagnosis criteria for cannabinoids hyperemesis syndrome
- History of regular cannabinoid use
- Cyclic N/V
- Generalized, diffuse abdominal pain
- Compulsive hot showers with symptom improvement
What does the pre-emetic (prodromal) phase of CHS look like?
Months to years
- Diffuse abdominal discomfort
- Agitation/stress
- Morning nausea, fear of vomiting
- Increased use of marijuana to treat
What does the hyper-emetic phase of CHS look like?
24-48 hours
- Cyclic episodes of N/V
- Diffuse, severe abdominal pain
What does the recovery phase of CHS look like?
Upon total cessation of cannabinoids
- Bowel regimes, fluids, electrolyte replacement
- Full resolution may take ~1 months
How can CHS be treated?
- Hot showers
- Capsaicin cream
- Ondansetron (haloperidol?)
- Benzodiazepines
- Supportive care (fluids, electrolytes)
What does the sympathomimetic toxidrome look like?
- Increased BP, HR, RR, Temperature
- Bowel sounds
- Pupil size increased
- Diaphoresis
- Agitated, hyperalert
- Tremors, seizures
How do you treat sympathomimetic toxicity?
Elimination (activated charcoal)
IV benzodiazepines
Anti-hypertensives
Fluids
Anti-psychotics
Electrolyte management
Ice baths
Sodium bicarbonate
What substances can we look out for in sympathomimetic toxicity?
- Cocaine
- Amphetamines
- Bath salts
- Pseudoephedrine
- Nootropic
How much cocaine is likely to be fatal?
1 gram
(1 line is 20-30 mg)
What are s/s of cocaine toxicity?
Euphoria, seizures, dysrhythmias, HTN
Coronary artery spasm MI?
What s/s might indicate cocaine adulteration with levimasole?
- Neutropenia
- Vasculitis
- Purpura
How is cocaine toxicity treated?
Supportive care, benzodiazepines
How does amphetamine toxicity present?
Agitation, seizures, hyperthermia, HTN, delirium
Similar to cocaine but longer lasting
How is amphetamine toxicity treated?
Benzodiazepines, barbiturates, anti-hypertensives (supportive care)
How does bath salts toxicity present?
Agitation, tachycardia, insomnia, paranoia, seizures, violent, unpredictable behavior
How is bath salts toxicity treated?
Benzodiazepines (clinical effects)
Intubations (airway protection)
Ice packs, cool fluids, antipyretics, benzos (hyperthermia)
Sodium bicarbonate, lidocaine (dysrhythmias)
Fluids (rhabdomyolysis)
Why are beta blocker and CCB toxicities more dangerous than other antihypertensives?
Hypotension WITH bradycardia
What does CCB toxicity look like?
Elevated blood sugar
What does BB toxicity look like?
Decreased mental status
What do non-DHP CCBs cause (as opposed to DHPs)?
Decreased HR and force of contraction
Which BB most commonly causes seizures?
Propranolol
Which type of BB has more effects?
Membrane stabilizing
(Acebutolol, Carvedilol, Betaxolol, Propranolol)
Which BB can cause Torsades de Pointes?
Sotalol
How can you treat CCB/BB toxicity?
GI decontamination (AC, WBI)
Fluids (isotonic)
Atropine (0.5-1 mg every 5 min for 3 doses, increases HR)
Calcium IV
Glucagon?
High-dose insulin and glucose**
How should high dose insulin euglycemia (HIET) therapy be given?
1 U/kg bolus, then 1-10 U/kg/hr
Keep glucose >100 mg/dL
Replace potassium as needed (2.8 - 3.5)
May take 30-60 min to work
When should you use glucagon and what can you expect?
It can be helpful after BB, given 3-5 mg and causes vomiting (avoid with altered mental status)
Which is the more potent form of calcium?
Calcium chloride is 3x more potent than calcium gluconate and causes sclerosing
What is the differential diagnostic lab that can point out CCBs?
Glucose (Ca2+ affects pancreas, less insulin)
What are adjunct treatments we can use for BB/CCBs?
Vasopressors (NE/EPI)
Inotropes (dobutamine, milrinone)
Cardiac pacing
Intralipid
VA-ECMO
What can we use to treat overdose of other antihypertensives?
Fluids*
Vasopressors
Atropine
What is special about clonidine toxicity presentation?
Transient HTN* and tachycardia* followed by an ABRUPT change to hypotension and bradycardia
- CNS and respiratory depression
How can we treat clonidine toxicity?
Naloxone 5-10 mg bolus +/- infusion (opioid receptor respiratory depression)
Supportive care
